Licorice root extract (Glycyrrhiza glabra, Glycyrrhiza uralensis) is a common ingredient found in many skin-lightening cosmeceuticals and is also used in the treatment of a wide variety of diseases even outside the scope of dermatology due to its anti-oxidant anti-inflammatory, antiviral, antimicrobial, and anticarcinogenic properties.

Licorice extract is obtained from the root of Glycyrrhia Glabra Linneva. The primary antioxidant and antiinflammatory compounds found in licorice root are the glycosides - glycyrrhizin and glycyrrizinic acid, flavonoids, and saponins.

Mechanism of Action

The main component of the hydrophobic fraction of licorice is glabridin. Glabridin has been shown to prevent UVB-induced pigmentation and to inhibit tyrosinase activity, superoxide anion production and cyclo-oxygenase activity. The depigmenting efficacy of glabridin has been shown by various researchers to be greater than that of hydroquinone. In cultured B16 murine melanoma cells, it inhibits tyrosinase activity at concentrations from 0.1 to 1.0 g ml-1, without affecting DNA synthesis. This suggests an influence of glabridin extract on both melanogenesis and inflammation of the skin.

Five different flavonoids were isolated from licorice to identify and characterize the active components in licorice as new tyrosinase inhibitors for depigmenting agents. The isolated flavonoids were identified as liquiritin, licuraside, isoliquiritin, liquiritigenin (from Glycyrrhiza uralensis Fisch) and licochalcone A (from Glycyrrhiza inflate Bat) and are all competitive inhibitors.

Liquiritin has no effect on tyrosinase; however, it causes depigmentation by other mechanisms, like melanin dispersion and removal and studies demonstrate that a 20% liquiritin cream applied at 1 g day-1 for 4 weeks is therapeutically effective in melisma.

Liquiritigenin activated the monophenolase activity as a cofactor. The inhibitory effect of licuraside, isoliquiritin and licochalcone A on diphenolase activity with L-DOPA as the substrate was much lower than that with L-tyrosine and have great potential for use as depigmenting agents. It was observed that glabrene and isoliquiritigenin (2′,4′,4-trihydroxychalcone) in the licorice extract can inhibit both mono- and diphenolase tyrosinase activities, and these effects on tyrosinase activity were dose-dependent and correlated to their ability to inhibit melanin formation in melanocytes.

Studies

In a recent study, a combination of licorice extract (0.4%), betamethasone (0.05%) and retinoic acid (0.05%) yielded an excellent skin lightening response in up to 70% of patients and topical application of 0.5% glabridin inhibited UVB-induced erythema and pigmentation in the skin of guinea-pigs.

Recently, studies of a Glycyrrhiza uralensis extract were performed by measuring the inhibitory activity of tyrosinase and melanin synthesis, which was shown to have no detectable effect on their DNA synthesis. Glycyrrhisoflavone and glyasperin C were identified as tyrosinase inhibitors for the first time. Glyasperin C showed a stronger tyrosinase inhibitory activity than glabridin and a moderate inhibition of melanin production and could make it a promising candidate in the design of skin-whitening agents. The combined analysis of SDS-polyacrylamide gel electrophoresis and DOPA staining on the large granule fraction of these cells disclosed that glabridin specifically decreased the activities of T1 and T3 tyrosinase isozymes. It was also shown that UVB-induced pigmentation and erythema in the skins of guinea-pigs were inhibited by topical applications of 0.5% glabridin.

Another study conducted in 20 Egyptian women showed that topical liquiritin cream (1g/day) for four weeks was both safe and effective in the treatment of melasma. Side effects were minimal. Further clinical studies are needed to evaluate the efficacy of licorice root extract in the treatment of pigmentary disorders.